Chitosan/dialdehyde starch hybrid in situ forming hydrogel for ocular delivery of betamethasone

Abstract

Ocular drug therapy remains to be a major pharmaceutical challenge due to the presence of ocular barriers. The development of novel ophthalmic delivery systems is an immense necessity to overcome such biological and physiological barriers. Hydrophilic gels are considered an ideal candidate for such purposes owing to their favorable characteristics such as rapid in situ gelation, biodegradability, biocompatibility, and high encapsulation capacity. In the current study, we report on the development of an in situ forming composite hydrogel formulated using natural polymers, including dialdehyde starch (DAS) and chitosan (CS), to deliver betamethasone to the eye. The modification of starch and composite hydrogel structure was evaluated by FT-IR spectroscopy. The effect of the different ratios of CS to DAS on the gelation time, surface microstructure morphology, swelling ratio, rheological behavior, and in vitro degradation was evaluated. Our findings demonstrated that the high content of DAS could result in fast gelation, improved mechanical strength, larger pore size, and optimized degradation with a fast in vitro and ex vivo release rate. Furthermore, the developed composite hydrogel displayed excellent biocompatibility in cell models in vitro. Altogether, the obtained data suggest that the developed hydrogel-based delivery system could be well suited for local administration of betamethasone to control ocular inflammation and consequent complications.